Development of an antibacterial activity enhancer that restores lost antibacterial activity

• Project/Area Number: 15K07932
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Hiroshima University (2016-2017); Okayama University (2015)
• Principal Investigator: Kuroda Teruo 広島大学, 医歯薬保健学研究科(薬), 教授 (80304327)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: topoisomerase / vancomycin / キノロン / バンコマイシン / MRSA / VRE / ペプチドグリカン

Outline of Final Research Achievements

The action mechanism of compound K on MRSA and VRE was investigated. Compound K inhibited topoisomerase IV of Staphylococcus aureus. However, this action mechanism was different from both ciprofloxacin and novobiocin, already known inhibitors of topoisomerase IV. Compound K also showed the combined effect with vancomycin. Expression of vancomycin resistant cluster genes was not inhibited with compound K, and exposure to compound K restored D-alanyl-D-alanine in VRE cells.

Research Products

• [Journal Article] Search for Novel Antibacterial Compounds and Targets (2017)
  • Author(s): 黒田照夫、小川和加野
  • Journal Title: YAKUGAKU ZASSHI Volume: 137 Issue: 4 Pages: 383-388
  • DOI: 10.1248/yakushi.16-00235-3
  • NAID: 130005529524
  • ISSN: 0031-6903, 1347-5231
  • Year and Date: 2017-04-01
  • Peer Reviewed / Open Access
• [Journal Article] Action mechanism of 6, 6'-dihydroxythiobinupharidine from Nuphar japonicum, which showed anti-MRSA and anti-VRE activities. (2015)
  • Author(s): Okamura S, Nishiyama E, Yamazaki T, Otsuka N, Taniguchi S, Ogawa W, Hatano T, Tsuchiya T, Kuroda T.
  • Journal Title: Biochim Biophys Acta. (General Subjects) Volume: 1850 Issue: 6 Pages: 1245-1252
  • DOI: 10.1016/j.bbagen.2015.02.012
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Novel anti-MRSA and anti-VRE compound from Nuphar japonicum (2017)
  • Author(s): Shinya Okamura, Eri Nishiyama, Tomohiro Yamazaki, Yuta Horikoshi, Nao Otsuka, Shoko Taniguchi, Wakano Ogawa, Tsutomu Hatano, Tomofusa Tsuchiya, Teruo Kuroda
  • Organizer: International Union of Microbiological Societies (IUMS) 2017
  • Int'l Joint Research
• [Presentation] 耐性菌に効く薬を創るということ (2016)
  • Author(s): 黒田照夫
  • Organizer: 第28回微生物シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2016-09-02
  • Invited
• [Presentation] 新規抗菌薬のシーズ発掘と標的探索 (2016)
  • Author(s): ○黒田照夫、小川和加野
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-03-27
• [Presentation] コウホネに含まれる抗MRSA, VRE活性を有する成分の単離と解析 (2015)
  • Author(s): ○岡村真弥, 西山永理, 山崎智弘,大塚菜緒, 谷口抄子, 波多野力, 小川和加野, 土屋友房, 黒田照夫
  • Organizer: 第27回微生物シンポジウム
  • Place of Presentation: 就実大学（岡山県岡山市）
  • Year and Date: 2015-09-04
• [Remarks] 広島大学薬学部微生物医薬品開発学
  • URL: https://www.hiroshima-u.ac.jp/pharm/research/lab/Microbiology